Our work of the past 3 years has given us a method that supports extracellular development of a complete asexual cycle of the erythrocytic stage of the major human malaria parasite Plasmodium falciparum (l). Just as the method for continuous in vitro propagation of this parasite in cell culture, reported from our laboratory in 1976 (26), made possible the extensive and brilliant work in molecular biology that has increased our understanding of the genetics of p falciparum and of the nature of chloroquine resistance, and has led to the identification of an array of candidate antigens that give promise for an effective erythrocytic stage vaccine (27), even so the further development of our axenic culture method will lead to deeper insights into the nature of the relationship between the parasite and its host erythrocyte. Our first aim therefore is to improve the axenic culture method. This will facilitate all further work. it would also provide for new approaches to vaccine development and studies of drug action. A second major aim will exploit the axenic development of merozoites into rings and early trophozoites to study the export from the parasites of specific proteins that in nature become associated with cisternae in the host erythrocyte or with the erythrocyte plasma membrane. Will these exported proteins form membranous structures in the acellular medium of axenic culture, where the rings are developing without a parasitophorous membrane? Comparative studies with ring-stage parasites that retain their parasitophorous membrane, prepared by lysis from host erythrocytes, may reveal a role for this membrane. Finally, the induction and development of gametocytes will be studied, with special reference to the greater formation of gametocytes in young erythrocytes. Results of the proposed work will contribute to understanding the physiology of the erythrocytic stages of malaria parasites and will bear on fundamental problems in intracellular parasitism.